Consensus summary report for CEPI/BC March 12–13, 2020 meeting: Assessment of risk of disease enhancement with COVID-19 vaccines

Abstract

A novel coronavirus (CoV), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 in Wuhan, China and has since spread as a global pandemic. Safe and effective vaccines are thus urgently needed to reduce the significant morbidity and mortality of Coronavirus Disease 2019 (COVID-19) disease and ease the major economic impact. There has been an unprecedented rapid response by vaccine developers with now over one hundred vaccine candidates in development and at least six having reached clinical trials. However, a major challenge during rapid development is to avoid safety issues both by thoughtful vaccine design and by thorough evaluation in a timely manner. A syndrome of ''disease enhancement" has been reported in the past for a few viral vaccines where those immunized suffered increased severity or death when they later encountered the virus or were found to have an increased frequency of infection. Animal models allowed scientists to determine the underlying mechanism for the former in the case of Respiratory syncytial virus (RSV) vaccine and have been utilized to design and screen new RSV vaccine candidates. Because some Middle East respiratory syndrome (MERS) and SARS-CoV-1 vaccines have shown evidence of disease enhancement in some animal models, this is a particular concern for SARS-CoV-2 vaccines. To address this challenge, the Coalition for Epidemic Preparedness Innovations (CEPI) and the Brighton Collaboration (BC) Safety Platform for Emergency vACcines (SPEAC) convened a scientific working meeting on March 12 and 13, 2020 of experts in the field of vaccine immunology and coronaviruses to consider what vaccine designs could reduce safety concerns

Assessing the Safety of COVID-19 Vaccines: A Primer

“…Studies of earlier SARS vaccines in animals identified two potential safety issues; antibody-dependent enhancement and cellular immunopathology. These have not been observed in human studies but flag potential responses for close examination and highlight the importance of selecting vaccine approaches and adjuvants that drive desirable responses [7].…”

Prospects for a safe COVID-19 vaccine

“…Among the potential risks raised in the context of COVID-19 vaccine development is whether the immune responses elicited by a vaccine could enhance SARS-CoV-2 acquisition or make the disease worse when infection occurs after vaccination. Recent commentaries have provided background and assessments of aspects of this question as it relates to COVID-19 vaccines (1,(5)(6)(7)(8)(9). Here, we review the relevant literature and evaluate the possibility of enhanced disease caused by COVID-19 vaccines.…”

What Would Jenner and Pasteur Have Done About COVID-19 Coronavirus? The Urges of a Vaccinologist

“…The second concern would be the promotion of an Antibody Disease Enhancement syndrome (ADE) by the vaccine. This is usually related to non-neutralizing antibodies, which determine an increased lung pathology and it was observed before in vaccines against RSV and Measles in the 1960's (53). Since SARS-CoV-1, MERS-CoV, and SARS-CoV-2 are phylogenetically related viruses that have caused epidemics over the last 16 years and ADE pathology was present for some SARSCoV-1 and MERS vaccine candidates in animal models, there is also a concern about the induction of ADE syndrome in humans vaccinated with SARS-CoV-2 vaccine candidates (53).…”